Diazepam binding inhibitor overexpression in mice causes hydrocephalus, decreases plasticity in excitatory synapses and impairs hippocampus-dependent learning
| Autor: | Leena Alhonen, Hanna Siiskonen, Selma K. Kaasinen, Mikko I. Kettunen, Juhana M. Hakumäki, Raimo Pussinen, Asla Pitkänen, Karlheinz Kiehne, Karl-Heinz Herzig, Sanna Oikari, Vootele Voikar, Veli-Pekka Korhonen, Juhani Jänne, Markku Penttonen, Tiina Wahlfors |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Genetically modified mouse
Male Kainic acid Long-Term Potentiation Hippocampus Mice Transgenic Biology Inhibitory postsynaptic potential Synaptic Transmission Cellular and Molecular Neuroscience chemistry.chemical_compound Mice Avoidance Learning Reaction Time Animals Molecular Biology Diazepam Binding Inhibitor Behavior Animal Learning Disabilities Dentate gyrus Long-term potentiation Cell Biology Magnetic Resonance Imaging chemistry Phosphopyruvate Hydratase Excitatory postsynaptic potential Female Neuroscience Diazepam binding inhibitor Hydrocephalus |
| Zdroj: | Molecular and cellular neurosciences. 34(2) |
| ISSN: | 1044-7431 |
| Popis: | Diazepam binding inhibitor (DBI) and its processing products are endogenous modulators of GABAA and linked to various brain disorders ranging from anxiety and drug dependence to epilepsy. To investigate the physiological role of endogenously expressed DBI in the brain we created a transgenic mouse line overexpressing DBI gene. Transgenic mice had a 37x increased protein expression and immunohistochemistry showed excessive glial expression in the infragranular region of the dentate gyrus. Transgenic animals had significantly larger lateral ventricles and decreased plasticity of excitatory synapses without affecting either inhibitory or excitatory synaptic transmission. In behavioral tests transgenic animals had no differences in motor and exploratory activity, yet impaired hippocampus-dependent learning and memory. Overexpression did not cause anxiety or proconflict behavior, nor influenced kainic acid or pentylenetetrazole induced seizure activity. Our transgenic mouse line demonstrates that endogenously overexpressed DBI impairs hippocampus-dependent learning without anxiety or proconflict behavior. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect